Diisopropylaniline → 2,6-Diisopropyl-N-((2-isopropylphenyl)(6-(2-((phenylamino)methyl)naphthalen-1-yl)pyridin-2-yl)methyl)aniline

Temperature

45 °C

Compound 5a (2.28 g, 5.18 mmol), tetrahydrofuran (50 mL), and 4 angstrom molecular sieves (ca. 20 mL) were combined. Then 2,6-diisopropylaniline (0.918 g, 5.18 mmol) and a catalytic amount of p-toluenesulfonic acid monohydrate (0.005 g, 0.03 mmol) were added. The mixture was heated to 45° C. for 14 hours. Then the mixture was filtered and fresh molecular sieves (ca. 15 mL) were added followed by additional p-toluenesulfonic acid monohydrate (0.005 g, 0.03 mmol). After heating at 50° C. for 2 hours the mixture was filtered and evaporated to a residue of the imine 6a. Then Et2O (30 mL) was added, and the resulting solution was cooled to −80° C. An Et2O (5 mL) solution of 2-isopropylphenyllithium (0.653 g, 5.18 mmol) was added dropwise. The mixture was then allowed to slowly warm to ambient temperature over a couple of hours. Then the mixture was poured into water (100 mL) and the organics were separated, dried over brine then magnesium sulfate, filtered, and evaporated to a residue. The residue was dissolved in chloroform (25 mL), and trifluoroacetic acid (10 mL) was added. The mixture was heated to reflux for 40 minutes, during which time gas evolved. The mixture was cooled to ambient temperature and 3 M NaOH (60 mL) was added. After stirring for several minutes, the organics were separated, dried over brine then magnesium sulfate, filtered through diatomaceous earth, and evaporated to yield the crude product. This was purified by chromatography on basic alumina using 5:1 hexanes:CH2Cl2 with an increasing gradient of ethyl acetate (1% to 10%). The product was isolated as a foam-like solid. For 1H NMR (in CD2Cl2) see FIG. 4.

1. filtrationThen the mixture was filtered
2. additionfresh molecular sieves (ca. 15 mL) were added
3. temperatureAfter heating at 50° C. for 2 hours the mixture
4. filtrationwas filtered
5. customevaporated to a residue of the imine 6a
6. additionThen Et2O (30 mL) was added
7. temperaturethe resulting solution was cooled to −80° C
8. temperatureto slowly warm to ambient temperature over a couple of hours
9. customthe organics were separated
10. dry with materialdried over brine
11. filtrationmagnesium sulfate, filtered
12. customevaporated to a residue
13. dissolutionThe residue was dissolved in chloroform (25 mL)
14. additiontrifluoroacetic acid (10 mL) was added
15. temperatureThe mixture was heated
16. temperatureto reflux for 40 minutes, during which time gas
17. temperatureThe mixture was cooled to ambient temperature
18. addition3 M NaOH (60 mL) was added
19. customthe organics were separated
20. dry with materialdried over brine
21. filtrationmagnesium sulfate, filtered through diatomaceous earth
22. customevaporated

ORD record

ord-d7ae223bac5940fc80583ec7c85c7462

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08394902B2